In Minneapolis, a man is jogging down a path at night. An overweight jogger runs after him, catches up, and runs past him. The first jogger continues on and finds the newcomer waiting for him. When he congratulates the man, the newcomer grabs his hand, thrust his hand into the jogger's chest, and pulls out his heart.
Sam and Dean are at a farmer's market and Dean is catching up on news. He finds an article about the stolen heart and another one six months earlier in the same city. Sam says that they have to deal with finding Kevin and the tablet, and then points out that he's buying fruit at the farm market. Dean reminds him that he quit for a year and asks if they should ignore cases so Sam can shop for produce.
Dean and Sam go Minneapolis and meet with Pike, the detective in charge of the case. Pike admits that there was no evidence and the victim was in town for a conference. He shows them video from the surveillance camera. They identified the newcomer, Paul Hayes, and questioned him. Paul said that he didn't know anything about it and he had no criminal record.
Paul is at home making a health smoothie when Sam and Dean come to visit and asks him what happened. The man admits that he didn't know the victim and that he didn't see anything. Sam points out that the jogger he outraced was younger than him and Paul explains that he had a health scare a year ago and it changed his life. He's been taking care of himself ever since. Once they realize that it's a dead end, Sam and Dean go to a bar and Dean says that he searched the place and didn't find anything unusual at Paul's place. He checks the Internet and discovers that there was another murder in Ames at the same time that Paul was being questioned. Six months ago there was another heart murder in Ames and the killer was a police officer, Arthur Swenson.
The brothers travel to Ames and talk to the killer's superior, Captain Levitt. The man swears by Swenson but admits that the victim, a pizza-delivery guy, was found dead in front of Swenson's house. Swenson was covered in blood and sobbing. Levitt confirms that Swenson was in court testifying when the murder in Minneapolis occurred. They go to see Swenson, who mutters the same phrase in a foreign language over and over again. The Winchesters try to get through to him and then sprinkle him with holy water but he doesn't burn.
That night, Swenson is in his cell, still chanting. He finally manages to pull a strut out of his bunk and drives the sharp end into his left eye.
At their motel, Sam plays back a recording of Swenson's muttering. Much to Sam's surprise, Dean has bought a translation app but it can't translate the words. The police call Sam and tell him about Swenson. Dean goes to the hospital and meets with Dr. Kashi, who explains that Swenson thoroughly removed his eye. Dean points out that Swenson had different colored eyes and Kashi confirms that Swenson was in an accident and received a transplanted eye, and the accident occurred exactly one year ago. Swenson cut out the transplanted eye, and Dean asks Kashi if she can trace the donor.
Dean returns to the motel later and Sam tells his brother that he checked Paul's medical records and confirmed that the man had a transplant a year ago. He suggests that the language was in a dead language and mailed it to Dr. Morrison. While they wait, Dean says they need to head to Boulder, CO, because that was where the next missing-heart murder was committed six months ago.
In Boulder, a man, Chick, waits outside a strip club. One of the strippers, Randa Monroe, comes out and Chick compliments her on her performance. She walks over and flirts with him before shoving him against a wall and ripping out his heart.
As they drive to Boulder, Dean says that the case is coming together and things are good between them. Sam is distracted but says that he isn't thinking about anything. His brother says that he's at his best hunting monsters with Sam, but Sam suggests that he doesn't need him and that he wants his time to count. Before they can argue it out, Dean gets a call from Kashi and then has her confirm that Paul received an organ from the same donor as Swenson. He also gets the name of the man in Colorado who received a new donor. The donor was Brick Holmes, a famous quarterback who died in a car accident and made eight donations to science.
Randa prepares a ritual, pointing her face with the blood from the heart. As she chants the same words as Swenson, Randa eats the heart and a burst of energy fills her body as her eyes glow red.
Sam and Dean arrive in Boulder and talk to Brick's mother, Eleanor. She explains that her son dedicated himself to physical perfection. They ask her about Brick's organ donor status and she admits that he probably signed up for it without even thinking about it. Dean points out that the accident had no known cause but Eleanor dismisses it as an accident. She doesn't know of any new interests that Brick had before he died and ushers them out because she has to go to a ceremony. As the brothers leave, Dean picks up a report about another heart-ripping death. Meanwhile, Eleanor watches them go as Randa comes downstairs. She wonders who Sam and Dean were and makes sure that Eleanor knows not to say anything. Eleanor assures her that she's not an idiot and Randa reminds her that she has Brick's heart inside her, giving her new life, and she moved to Boulder to be near Eleanor and watch over her. She says that Brick needs them and warns Eleanor to keep the secret.
At the motel, Sam checks in with Dr. Morrison. He informs Sam that Swenson was speaking in ancient Mayan, saying "The divine god Cacao is born." Cacao is the Mayan god of maize and the most powerful deity in the pantheon. Dean warns that the next victim, Jimmy Yang, is in Phoenix and has disappeared. He also received an email to Sam about going back to college and Sam says that he's just looking for options. Dean figures that Eleanor is the key but warns Sam that they're not done discussing his future.
The brothers break into Eleanor's home and search the place. Sam checks Brick's closet and finds the dress that Eleanor was wearing when she talked to them. Dean continues looking and finds a hidden door. Inside is a room filled with Brick's sporting memorabilia. There are trophies for all kinds of sports, not just football, and Sam realizes that Brick admired all athletes. Dean finds a box with old letters, written to Betsy. They date back to the 1940s and in each one, Brick mentions his participation in different sports. In one recent letter, Brick says that he's grown tired of it all.
Sam and Dean go back to their motel and Sam confirms that the people that won all of the trophies looked the same. They figure that Brick was at least 95 years old and never aged. Dean suggests that in Mayan tradition, their athletes were treated as kings and the athletes ate human hearts to gain superhuman powers. The brothers figure that Brick made a deal with Cacao and may be a 900-year-old Aztec who has kept himself young. Sam figures that everyone who received one of Brick's organs received the same curse/deal but Swenson broke under the stress. Sam finds a photo of Brick with Betsy... Eleanor.
The Winchesters go back to see Eleanor and tell her that they know she's Betsy. They explain what has been happening and she swears that she didn't know about the murders. Eleanor thought that the sacrifices would end when Brick died, and Dean asks for her help so she can honor his legacy. Eleanor tells them that Inyo was 1100 years old and didn't want to lose his perfection. He made a deal with Cacao in return for two sacrifices a year at harvest and planting. She loved him so much that she overlooked what he had to do. Every ten years they went underground when it became clear Brick wasn't aging. When she entered her 40s, she posed as Brick's mother instead. When Brick realized that she was going to die, he couldn't bear the thought of life without her and committed suicide. Dean says that there are eight killers that they have to deal with, but Eleanor explains that the heart was the focus of the ceremony. If they stop Brick's beating heart then they can end the curse. Sam asks Eleanor if she knows who has the heart.
Eleanor sends them to the strip club where Randa works and the brothers take out a large knife and go inside. The place is closed during the day and they make it to the stage. The lights come on and Randa steps out. She figures that Eleanor gave her up and warns the brothers that it's not going to end well for them. When they draw their knives, Randa says that "they" won't let them do it. The remaining organ recipients, including Paul, attack the brothers and knock Sam out. They pin Dean to the stage and Randa explains that she was a weak little girl until her heart gave out and she received Brick's heart. Now she thrives on the feeling of being a warrior. She rips open Dean's shirt and promises him that she'll do it slow.
As Randa starts to push into Dean's chest, Sam revives and knocks Paul off. Dean stabs Randa in the heart with his knife and she glows with energy. The organs burn out of the other recipients and Randa finally collapses as well.
Later, the Winchesters go to see Eleanor and tell her that it's finally over. She's glad to be at peace and they hit the road. Dean asks Sam if it feels good and Sam says that he doesn't feel like a warrior. Once they've found Kevin and the tablet, he's done. Dean doesn't believe it, but Sam explains that in the year that he took off, he had a normal life. As they talk, Sam remembers Amelia throwing him a birthday picnic, complete with a cake.